{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T12:14:47Z","timestamp":1791807287213,"version":"4.3.4"},"reference-count":47,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2021,10,21]],"date-time":"2021-10-21T00:00:00Z","timestamp":1634774400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Korea Health Technology R&amp;D Project through the Korea Health Industry Development Institute, funded by the Ministry of Health &amp; Welfare, South Korea","award":["grant number HI16C1559"],"award-info":[{"award-number":["grant number HI16C1559"]}]},{"name":"National Research Foundation of Korea (NRF) grant funded by the Korea government","award":["NRF-2019R1C1C1004017"],"award-info":[{"award-number":["NRF-2019R1C1C1004017"]}]},{"name":"National Research Foundation of Korea (NRF) grant funded by the Korea government","award":["NRF-2019R1C1C1005658"],"award-info":[{"award-number":["NRF-2019R1C1C1005658"]}]},{"name":"National Research Foundation of Korea (NRF) grant funded by the Korea government","award":["NRF-2020R1I1A1A01073917"],"award-info":[{"award-number":["NRF-2020R1I1A1A01073917"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Intervertebral discs (IVDs) have poor nutrient diffusion, because the nucleus pulposus (NP) lacks direct vascular supply and likely generates adenosine triphosphate by anaerobic glycolysis. Regulation of glycolysis is mediated by hypoxia-inducible factor-1\u03b1 (HIF-1\u03b1), a transcription factor that responds to local oxygen tension. Constitutively active HIF-1\u03b1 (CA HIF-1\u03b1) was created by point mutation and determined the protective role of HIF-1\u03b1 in IVD degeneration. Under fluoroscopy, rat caudal IVD segments were stabbed by a needle puncture, and pcDNA3- HIF-1\u03b1 wild-type (WT) or pcDNA3-CA HIF-1\u03b1 was transfected into NP cell lines. The constitutive activity of CA HIF-1\u03b1 was analyzed using a luciferase assay after cell lysis. Next, IVD tissue samples were retrieved from five patients with degenerative lumbar spinal stenosis at the time of surgery, and NP cells were cultured. NP cells were transfected with CA HIF-1\u03b1, and relevant gene expression was measured. HIF-1\u03b1 protein levels in the nucleus were significantly higher, and transcriptional activity was 10.3-fold higher in NP cells with CA HIF-1\u03b1 than in those with HIF-1\u03b1 WT. Gene transfer of CA HIF-1\u03b1 into NP cells enhanced the expression of Glut-1, Glut-3, aggrecan, type II collagen, and Sox9. Moreover, CA HIF-1\u03b1 reduced the apoptosis of NP cells induced by the Fas ligand. The HIF-1\u03b1 and collagen 2 expression levels were notably increased in the NP cells of the CA HIF-1\u03b1 transfected segments in histology and immunohistochemistry study. Collectively, these results suggest that activation of HIF-1\u03b1 signaling pathway may play a protective role against IVD degeneration and could be used as a future therapeutic agent.<\/jats:p>","DOI":"10.3390\/ijms222111355","type":"journal-article","created":{"date-parts":[[2021,10,22]],"date-time":"2021-10-22T00:22:02Z","timestamp":1634862122000},"page":"11355","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["Activation of Hypoxia-Inducible Factor-1\u03b1 Signaling Pathway Has the Protective Effect of Intervertebral Disc Degeneration"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0186-5834","authenticated-orcid":false,"given":"Jin-Woo","family":"Kim","sequence":"first","affiliation":[{"name":"Department of Orthopaedic Surgery, Nowon Eulji Medical Center, Eulji University, Seoul 01830, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5359-715X","authenticated-orcid":false,"given":"Hyun-Ju","family":"An","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery, CHA Bundang Medical Center, CHA University, 59 Yatap-ro, Bundang-gu, Seongnam-si 13496, Gyeonggi-do, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"HyunJeong","family":"Yeo","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery, CHA Bundang Medical Center, CHA University, 59 Yatap-ro, Bundang-gu, Seongnam-si 13496, Gyeonggi-do, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunhui","family":"Jeong","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery, CHA Bundang Medical Center, CHA University, 59 Yatap-ro, Bundang-gu, Seongnam-si 13496, Gyeonggi-do, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"HyeonHae","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery, CHA Bundang Medical Center, CHA University, 59 Yatap-ro, Bundang-gu, Seongnam-si 13496, Gyeonggi-do, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jusung","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery, CHA Bundang Medical Center, CHA University, 59 Yatap-ro, Bundang-gu, Seongnam-si 13496, Gyeonggi-do, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kisik","family":"Nam","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery, CHA Bundang Medical Center, CHA University, 59 Yatap-ro, Bundang-gu, Seongnam-si 13496, Gyeonggi-do, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jongheon","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery, Nowon Eulji Medical Center, Eulji University, Seoul 01830, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dong-Eun","family":"Shin","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery, CHA Bundang Medical Center, CHA University, 59 Yatap-ro, Bundang-gu, Seongnam-si 13496, Gyeonggi-do, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soonchul","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery, CHA Bundang Medical Center, CHA University, 59 Yatap-ro, Bundang-gu, Seongnam-si 13496, Gyeonggi-do, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,10,21]]},"reference":[{"key":"ref_1","first-page":"1033","article-title":"Intervertebral disc biology, degeneration and novel tissue engineering and regenerative medicine therapies","volume":"22","author":"Richardson","year":"2007","journal-title":"Histol. 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